Sodium valproate enhancement of gamma-aminobutyric acid (GABA) inhibition: electrophysiological evidence for anticonvulsant activity.
The purpose of this study was to gain further insight into the mechanism of action of the anticonvulsant sodium valproate. The effects of valproate on spontaneous neuronal activity and its interaction with locally applied gamma-aminobutyric acid (GABA) were assessed in the rat cerebral cortex. Extracellular neuronal potentials were recorded using standard procedures. Valproate, glycine, GABA and bicuculline methiodide were applied through microiontophoresis. Valproate at 30, 50, and 100 nA did not affect the spontaneous activity of the majority of cells (21), increased the firing rate in four and slowed right cells. When applied simultaneously with GABA, valproate significantly enhanced GABA inhibition in a dose-related manner. Bicuculline methiodide antagonized the combined effects of valproate and GABA. Glycine inhibitions were not significantly enhanced by valproate. Our results indicate that valproate enhances GABA inhibition in the cerebral cortex, an action which is independent of its effect on spontaneous activity. The specificity of valproate for GABA suggests that this interaction may be an important mechanism through which valproate exerts its anticonvulsant properties.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants; D002540:Cerebral Cortex / Q000187:drug effects*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D051381:Rats; D014635:Valproic Acid / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid